Atopic dermatitis is a kind of hypersensitivity associated with dermal inflammation such as eczema, among the diseases related to an allergic reaction. It is associated with physiological abnormalities including skin dryness and barrier dysfunction caused by stratum corneum abnormality. Various non-specific irritation responses and specific allergic reactions are involved in the development of atopic dermatitis.
Atopic dermatitis is considered to occur by complicated interactions of genetic predisposition, exposure to environment and immunological mechanisms. Due to uncertain pathogenic mechanism, the treatment of atopic dermatitis is limited to application of anti-inflammatory topical medicaments such as corticosteroids and calcineurin inhibitors. However, these compounds cannot completely suppress the onset of atopic dermatitis. No satisfying therapy of atopic dermatitis has been established.
Mast cells are known to cause type I allergic reaction via IgE to mediate many diseases such as atopic dermatitis. Therefore, it is expected that suppression of the function of mast cells enables the treatment of these diseases. The mast cells are known to produce many inflammatory mediators, and be activated by various stimuli to degranulate, thereby releasing such inflammatory mediators. For example, mast cells contain various chemical mediators including histamine. When mast cells recognize an antigen, said recognition triggers activation of membrane enzymes on the mast cells, resulting in the release of granules containing histamine and tryptase. In addition, activation of the cell membrane enzymes increases production and metabolism of arachidonate (arachidonate cascade) and releases its metabolites, leukotriene, platelet activating factor (PAF), prostaglandin thromboxane A2 and the like, from the cell membrane.
Meanwhile, a kind of carotenoids, fucoxanthin, has been considered to act as a provitamin A in a living body and is known to have an antioxidant action suppressing the production of reactive oxygen species (ROS) by oxidation stress in cultured dermal cells. In addition, Kawashima (JP 2012-254959 A) teaches that fucoxanthin suppresses IL-17 production and Th-17 cell differentiation and proposes use of food and drink or an oral drug comprising fucoxanthin or a derivative thereof for the prophylaxis or improvement of Th-17 diseases. Yamada (JP 2009-108022 A) discloses that oral intake of fucoxanthin results in an anti-allergic effect.
However, when fucoxanthin is orally ingested, it is metabolized via liver and mostly functions as a vitamin A-like substance. Vitamin A improves barrier function of mucosal epithelial cells, and degrades and detoxifies lipoperoxides. Since one of vitamins A, retinoic acid, also has a suppressive action against Th-17 cell differentiation, it is strongly suggested that the effects of oral intake of fucoxanthin described in the above-mentioned patent documents are based on its provitamin A activity, namely the active ingredients are its metabolites, vitamin A-like substances.
Yamada (supra) also evaluates the anti-allergic effect of fucoxanthin by using a decrease of serum eosinophils as an index, but it fails to disclose local effects (in particular, itch suppression effect) of fucoxanthin on the skin of hives or atopic dermatitis. Yamada also fails to teach or suggest effects of fucoxanthin on mast cells.